RNAi-mediated Heterochromatin Assembly in Fission Yeast

Abstract

The organization of DNA into heterochromatin domains is critical for a variety of chromosomal functions, including genesilencing, recombination suppression, and chromosome segregation. In fission yeast, factors involved in the RNAi pathwaysuch as Argonaute, Dicer, and RNA-dependent RNA polymerase are required for assembly of heterochromatin structures. TheRNAi Argonaute-containing RITS complex and RNA-dependent RNA polymerase localize throughout heterochromatindomains. These factors are important components of a self-reinforcing loop mechanism operating in cis to process repeat transcriptsinto siRNAs, which involve in heterochromatin assembly. In this paper, we describe our results suggesting that slicingof repeat transcripts by the Argonaute is an important step in their conversion into siRNAs and heterochromatic silencing.Mutations in conserved residues known to be essential for slicer activity of Argonautes result in loss of siRNAs correspondingto centromeric repeats, accumulation of repeat transcripts, and defects in heterochromatin assembly. We also discuss ourrecent finding that heterochromatin proteins such as Swi6/HP1 serve as a platform that could recruit both silencing and antisilencingfactors to heterochromatic loci.